Preparation of biopolymer arrays

• US 6,372,483 B2
• Filed: 03/28/2001
• Issued: 04/16/2002
• Est. Priority Date: 04/30/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Schleifer, Arthur, Caren, Michael P., Schembri, Carol T.
• Primary Examiner(s): Siew, Jeffrey
• Application Number:
  US09/820,476
• Publication Number:
  US 20010010916A1
• Time in Patent Office: 384 Days
• Field of Search: 435/6, 435/7.1, 435/91.1, 435/91.2, 435/283.1, 435/285.1, 435/287.2, 536/22.1, 536/23.1, 536/24.3, 536/24.31, 536/24.32, 536/24.33, 347/1, 347/6, 347/20, 347/25
• US Class Current: 435/287.1
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00729 Peptide nucleic acids [PNA]
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 40/14 : Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/1041 : Ink-jet like dispensers
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array

Abstract

A method and apparatus for fabricating an array of biopolymers on a substrate using a biopolymer or biomonomer fluid, and using a fluid dispensing head. The head has at least one jet which can dispense droplets onto a substrate, the jet including a chamber with an orifice, and including an ejector which, when activated, causes a droplet to be ejected from the orifice. The method includes positioning the head with the orifice facing the substrate. Multiple droplets of the biopolymer or biomonomer fluid are dispensed from the head orifice so as to form an array of droplets on the substrate. A gas flow is directed through a venturi which has a throat opening communicating with the dispensing head chamber. A venturi control valve which particularly communicate with an outlet of the venturi, is adjusted to alter the chamber pressure. The venturi may be driven by a source of inert anhydrous compressed gas which assists in maintaining fluid in the head isolated from moisture.

Claims

1. An apparatus for fabricating an array of biopolymers on a substrate, comprising:

(a) a substrate station on which the substrate can be mounted;

(b) a dispensing head having;

at least one jet which can dispense droplets onto a substrate, the jet including a chamber with an orifice, and including an ejector which, when activated, causes a droplet to be ejected from the orifice;

(c) a positioning system to move at least one of the dispensing head and mounted substrate with respect to the other so that multiple droplets dispensed from the head onto the substrate will form an array thereon;

(d) a venturi having an inlet and an outlet, and a throat opening communicating with the chamber; and

(e) an adjustable venturi outlet control valve communicating with the venturi outlet so that selectable pressure can be applied to the head chamber by adjustment of the outlet control valve.

2. An apparatus according to claim 1 wherein the venturi outlet control valve can be adjusted to apply positive or negative pressure to the dispensing head chamber.

3. An apparatus according to claim 1 additionally comprising a load station spaced from the substrate station to retain multiple biopolymer or polymerizable biomonomer reagent solutions for loading into the head.

4. An apparatus according to claim 1 wherein each fluid droplet has a volume of from 0.1 to 1000 pL.

5. An apparatus according to claim 1 additionally comprising a source of anhydrous compressed gas communicating with the venturi inlet.

6. An apparatus according to claim 1 wherein the venturi outlet control valve is adjustable to provide selectable different negative pressures to the chamber.

7. An apparatus according to claim 1 additionally comprising:

a purge station spaced from the substrate station; and

a control processor which operates the positioning system to selectively position the head facing any one of the stations, and which adjusts the venturi outlet control valve to a restricted position so as to provide, when the head is facing the purge station, a positive pressure to the chamber from the venturi throat opening to purge fluid from the dispensing head.

8. An apparatus according to claim 1 additionally comprising:

a load station spaced from the substrate station;

a control processor which operates the positioning system to selectively position the head facing any one of the stations, and which adjusts the venturi outlet control valve so as to provide, when the head is facing the load station, a negative pressure to the chamber from the venturi throat opening to draw fluid positioned adjacent the orifice into the chamber through the orifice.

9. An apparatus according to claim 1 additionally comprising:

a load station and a purge station which are spaced from the substrate station; and

a control processor which operates the positioning system to selectively position the dispensing head facing any one of the stations; and

wherein;

the control processor adjusts the venturi outlet control valve to apply negative pressure to the chamber from the venturi throat opening when the dispensing head is facing the load station, so as to draw fluid positioned adjacent the orifice into the chamber through the orifice; and

the control processor adjusts the venturi outlet control valve so that positive pressure is applied to the chamber from the venturi throat opening when the dispensing head is facing the purge location, to force out any fluid in the head.

10. An apparatus according to claim 1 wherein the head has multiple pulse jets with orifices on a common front face of the head.

11. An apparatus for fabricating an array of biopolymers on a substrate, comprising:

(a) a substrate station at which the substrate can be mounted;

(b) a dispensing head having;

at least one jet which can dispense droplets onto a substrate, the jet including a chamber with an orifice, and including an ejector which, when activated, causes a droplet to be ejected from the orifice;

(c) a positioning system to move at least one of the dispensing head and mounted substrate with respect to the other so that multiple droplets dispensed from the head onto the substrate will form an array thereon;

(d) a venturi having an inlet and an outlet, and a throat opening communicating with the chamber; and

(e) a source of anhydrous compressed gas communicating with the venturi pressurized gas inlet.

12. An apparatus according to claim 11 additionally comprising a valve to adjust the gas flow rate through the venturi.

13. An apparatus according to claim 11 wherein the valve is on an inlet side of the venturi.

14. An apparatus according to claim 11 wherein the head has multiple pulse jets with orifices on a common front face of the head.

15. An apparatus for fabricating an array of biopolymers on a substrate, comprising:

(a) a substrate station at which the substrate can be mounted;

(b) a dispensing head having;

at least one jet which can dispense droplets onto a substrate, the jet including a chamber with an orifice, and including an ejector which, when activated, causes a droplet to be ejected from the orifice;

(c) an enclosure about the substrate station and dispensing head so that the head and substrate station can be maintained in a controlled atmosphere;

(d) a positioning system to move at least one of the dispensing head and mounted substrate with respect to the other so that multiple droplets dispensed from the head onto the substrate will form an array thereon;

(d) a venturi having an inlet and an outlet, and a throat opening communicating with the chamber; and

(e) a valve to control gas flow rate through the venturi.